The aim of this proposal is to develop new and selective chemical methods for the total synthesis and clinical analysis of naturally-occurring polyamines, their conjugates, secondary metabolites, macrocyclic derivatives and structural analogs for chemotherapeutic use. Polyamine-linked metabolic disorders include cystic fibrosis, atherosclerosis, MS, sickle-cell disease and other illnesses. Cyclic derivatives of tri- and tetramines enable selective transformations of select polyamine nitrogens, consequently the swift, convergent assembly of such structures. Substrates for the study of polyamine oxidative metabolism are described.